"Adult onset" common variable immune deficiency was previously shown to be genetically determined, using lymphocyte DNA and RNA synthesis in synchronous cell culture. Heterogeneity in this group was also shown by familial Gm(a)/(f) imbalance and sequence studies of light-chain V regions. The Wiskott-Aldrich syndrome (WAS) has been shown to include at least two distinct forms, one of which is associated with a defect in monocyte IgG receptors. Heterogeneity in WAS and in other genetically determined immune defects with respect to response to therapy has been observed and is under study, and heterogeneity in other immune deficiencies (e.g., hyper-IgM with immune deficiency) has been observed both in terms of clinical and/or genetic features and on the basis of laboratory tests of immune function. The quantitative test for "active" T-cell rosettes previously developed by us has proved extremely valuable for diagnosis and for monitoring the frequency of therapy of T-cell defects. Dialyzable transfer factor (TFd), which was shown earlier to produce a six-month prophylaxis of recurrent infections in 18 WAS patients with defective monocyte receptors (but not in patients without the defect), accompanied by a rise in active rosettes and production of leukocyte migration inhibitory factor (LIF) and macrophage migration inhibitory factor (MIF), has been applied in several other types of known or suspected genetic immune defects, both "broad-spectrum" and "antigen-selective".